Our overall objective is to better understand the genetic and environmental determinants of bladder cancer in humans. Specifically, we aim (1) to determine whether genetic factors may alter risk of bladder cancer associated with cigarette smoking. We will focus on the possible roles of several genetically regulated enzymes involved in the activation or inactivation of carcinogens present in cigarette smoke, including N- acetyltransferase, cytochrome P4501A2 (CYP1A2), and glutathione S- transferase M1 (GSTM1). We will determine if the slow acetylation and rapid oxidation phenotypes, and the homozygous null GSTM1 genotype are risk factors for bladder cancer in high- (Los Angeles whites) and low- (Chinese) risk populations; (2) to assess other recently suggested or inadequately studied risk or protective factors for bladder cancer, including (a) passive smoke exposure, (b) vitamin A/carotenoid intake, (c) vitamin C intake, (d) frequency of micturition, (e) long-term use of analgesics, and (f) use of hair dyes; (3) to further understand the relationship between smoking behavior and risk of bladder cancer in populations at varying risk of bladder cancer. As an objective assessment of biologically effective aromatic amine exposure from cigarettes or other sources, we will assess levels of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts in all cases and controls. We will also measure levels of urinary cotinine in all study subjects; and (4) to compare risk factors in high versus low risk populations and to assess the impact of comparable levels of exposure to these risk factors on level of risk in these populations. A case-control study of bladder cancer involving several biomarker measurements is proposed. Cases will be histologically confirmed incident cases of bladder cancer among Los Angeles whites/blacks and Shanghai Chinese aged 25-64 years. Controls will be selected from the neighborhoods where the cases are living at the time of cancer diagnosis. Each control will be individually matched to the index case on race, sex, and date of birth (within 5 years). About 800 cases and 800 controls will be recruited in Los Angeles (blood and urine specimens will be available on about 550 cases and 550 controls). In Shanghai, we will complete interviews on about 560 cases and 560 controls, and collect blood and urine specimens from about 550 cases and 550 controls.